Abstract
Triacylglycerol (TAG) hydrolysis, membrane lipid biosynthesis, and lipid turnover are largely interlinked processes. In yeast, TAG is mobilized by three TAG lipases named Tgl3p, Tgl4p, and Tgl5p, which are localized to lipid particles/droplets. These TAG lipases posses a conserved GXSXG motif that is characteristic of hydrolytic enzymes. Here, we demonstrated that the yeast TAG lipase Tgl4p, the functional ortholog of the adipose TAG lipase, ATGL, catalyzes multiple functions in lipid metabolism. An extended domain and motif search analysis revealed that Tgl4p bears not only a lipase consensus domain but also a conserved motif for calcium-independent phospholipase A(2). We show that Tgl4p exhibits TAG lipase, steryl ester hydrolase, and phospholipase A(2) activities, but surprisingly it also catalyzed the acyl-CoA-dependent acylation of lysophosphatidic acid to phosphatidic acid (PA). Heterologous overexpression of Tgl4p in Pichia pastoris increased total phospholipid and specifically PA synthesis. Moreover, deletion of TGL4 in Saccharomyces cerevisiae showed an altered pattern of phosphatidylcholine and PA molecular species. Altogether, our data suggest that yeast Tgl4p functions as a hydrolytic enzyme in lipid degradation but also contributes to fatty acid channeling and phospholipid remodeling.
Highlights
Lysophospholipid acyltransferases and transacylases are involved in the remodeling of phospholipids
Fatty acyl chains in the sn-2 position of the glycerol backbone can be removed by specific phospholipases A2 (PLA2),2 which leads to the formation of 1-acyl lysophospholipids
Dual Signature Motifs in Tgl4p—Previously the yeast protein Tgl4p had been reported as TAG lipase and an ortholog of the mammalian ATGL
Summary
Lysophospholipid acyltransferases and transacylases are involved in the remodeling of phospholipids. Fatty acyl chains in the sn-2 position of the glycerol backbone can be removed by specific phospholipases A2 (PLA2), which leads to the formation of 1-acyl lysophospholipids. These intermediates are reacylated by lysophospholipid acyltransferases in the course of remodeling processes [17, 18]. EUROSCARF collection, Frankfurt, Germany EUROSCARF collection, Frankfurt, Germany Invitrogen Ref. 41 This study in PC remodeling and maintaining PC molecular species with specific acyl chains at different ratios [30, 31] This far, three yeast phospholipases B have been identified and characterized. The possible function of these enzymes as PLA2 has never been addressed
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